Journal article
Inhibition of CXCR4-mediated G protein stimulation in the cortex and the hippocampus of morphine-treated animals
Journal of neurovirology, Vol.13
01 Jan 2007
Abstract
The chemokine CXCL12/SDF-la and its specific receptor (CXCR4) have been increasingly studied in the CNS due to their critical roles in neuronal patterning and survival. CXCR4 is also one of the major HIV-1 co-receptors and is involved in HIV neuropathogenesis. Recent evidence suggests that drugs of abuse, including opiates, can facilitate progression to neuroAIDS. The goal of this study is to establish whether in vivo morphine treatment alters CXCR4 coupling to G proteins. This hypothesis is based on previous studies suggesting an interaction between CXCR4 and mu-opioid receptors in cultured neurons and brain slices. The [35S]GTPgammaS incorporation assay was used to determine CXCL12-induced stimulation of GTP "binding" in various brain areas. Rat pups (8-14 days old) were used for these experiments since they showed similar regional distribution of G protein stimulation in response to CXCL12 and MOR agonists. Animals were treated with Morphine for short (1-24 hrs) or relatively long (3-5 days) time periods and GTPgammaS autoradiography was performed at different times. Brain sections from vehicle and morphine-treated animals were incubated with saline or CXCL12 (1-100nM) in the presence or absence of the CXCR4 antagonist AMD3100 (100ng/ml). The data show a reduction in CXCR4 coupling to G proteins after morphine pre-treatment in several brain areas, including cortex and hippocampus. These findings support the hypothesis that opioids may alter CXCR4 function and are supported by our studies with cultured cortical neurons. We propose that impairment of CXCR4 by opiates contribute to the neurological deficits associated with HIV infection.
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Details
- Title
- Inhibition of CXCR4-mediated G protein stimulation in the cortex and the hippocampus of morphine-treated animals
- Creators
- S BurbassiR SenguptaK SimanskyO Meucci
- Publication Details
- Journal of neurovirology, Vol.13
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Identifiers
- 991019170359304721